Fluorinated poly(ether)s end-capped with polymerizable cationic hydrophilic groups

ABSTRACT

The present invention relates to polymeric compositions useful in the manufacture of biocompatible medical devices. More particularly, the present invention relates to certain cationic monomers capable of polymerization to form polymeric compositions having desirable physical characteristics useful in the manufacture of ophthalmic devices. The polymer compositions comprise polymerized fluorinated polyether monomer end-capped with ethylenically unsaturated cationic hydrophilic groups.

CROSS-REFERENCE TO RELATED APPLICATIONS

None

FIELD

The present invention relates to polymeric compositions useful in themanufacture of biocompatible medical devices. More particularly, thepresent invention relates to certain fluorinated poly(ether)s end-cappedwith polymerizable cationic hydrophilic groups capable of polymerizationto form polymeric compositions having desirable physical characteristicsuseful in the manufacture of ophthalmic devices.

BACKGROUND AND SUMMARY

Fluorinated poly(ether)s (FPEs) are a unique class of chemically inert,low modulus materials that have characteristically high oxygenpermeability. FPEs functionalized with polymerizable methacrylateend-groups have been pursued for use in contact lens materials to takeadvantage of the high Dk but have not been incorporated into acommercial lens presumably due to the very hydrophobic nature of thefluorinated backbone and resulting incompatibility with other monomersand/or additives resulting in a non-wetting, uncomfortable lens.

The present invention provides novel fluorinated polyethers chemicallymodified such that the end-groups contain hydrophilic, ionicpolymerizable groups. The ionic groups will impart hydrophilicity to theFPE and dramatically improve compatibility with additional hydrophilicmonomers and other additives, increase the water contents fromtraditional fluorinated materials, and therefore result in a lens withboth the comfort of a traditional hydrogel and the oxygen permeabilityof a fluorinated material.

BRIEF DESCRIPTION OF THE DRAWINGS

None

DETAILED DESCRIPTION

The term “monomer” and like terms as used herein denote relatively lowmolecular weight compounds that are polymerizable by, for example, freeradical polymerization, as well as higher molecular weight compoundsalso referred to as “prepolymers”, “macromonomers”, and related terms.

The term “(meth)” as used herein denotes an optional methyl substituent.Accordingly, terms such as “(meth)acrylate” denotes either methacrylateor acrylate, and “(meth)acrylic acid” denotes either methacrylic acid oracrylic acid.

As set forth herein, FPEs (Solvay Solexis) are functionalized to containionic, polymerizable vinyl end-groups.

In a first aspect, the invention relates to monomers of formula (I):

wherein L can be the same or different and is selected from the groupconsisting of a bond, hydrogen, urethanes, carbonates, carbamates,carboxyl ureidos, sulfonyls, a straight or branched C1-C30 alkyl group,a C1-C30 fluoroalkyl group, a C1-C20 ester-containing group, an alkylether, cycloalkyl ether, cycloalkenyl ether, aryl ether, arylalkylether, a polyether containing group, an ureido group, an amide group, anamine group, a substituted or unsubstituted C1-C30 alkoxy group, asubstituted or unsubstituted C3-C30 cycloalkyl group, a substituted orunsubstituted C3-C30 cycloalkylalkyl group, a substituted orunsubstituted C3-C30 cycloalkenyl group, a substituted or unsubstitutedC5-C30 aryl group, a substituted or unsubstituted C5-C30 arylalkylgroup, a substituted or unsubstituted C5-C30 heteroaryl group, asubstituted or unsubstituted C3-C30 heterocyclic ring, a substituted orunsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, a C5-C30 fluoroaryl group,or a hydroxyl substituted alkyl ether and combinations thereof.

X⁻ is at least a single charged counter ion. Examples of single chargecounter ions include the group consisting of Cl⁻, Br⁻, I⁻, CF₃CO₂ ⁻,CH₃CO₂ ⁻, HCO₃ ⁻, CH₃SO₄ ⁻, p-toluenesulfonate, HSO₄ ⁻, H₂PO₄ ⁻, NO₃ ⁻,and CH₃CH(OH)CO₂ ⁻. Examples of dual charged counter ions would includeSO₄ ²⁻, CO₃ ²⁻ and HPO₄ ²⁻. Other charged counter ions would be obviousto one of ordinary skill in the art. It should be understood that aresidual amount of counter ion may be present in the hydrated product.Therefore, the use of toxic counter ions is to be discouraged. Likewise,it should be understood that, for a singularly charged counter ion, theratio of counter ion and quaternary siloxanyl will be 1:1. Counter ionsof greater negative charge will result in differing ratios based uponthe total charge of the counter ion.

m is 1-5, and n is 1-10,000; each Rf is independently hydrogen,fluorine, a C5-C30 fluoroaryl group, a C1-C30 fluoroalkyl group, orcombinations thereof with the proviso that at least some, but not all,Rf is hydrogen; R is independently hydrogen, a straight or branchedC1-C30 alkyl group, a C1-C20 ester-containing group, an alkyl ether,cycloalkyl ether, cycloalkenyl ether, aryl ether, arylalkyl ether, apolyether containing group, an ureido group, an amide group, an aminegroup, a substituted or unsubstituted C1-C30 alkoxy group, a substitutedor unsubstituted C3-C30 cycloalkyl group, a substituted or unsubstitutedC3-C30 cycloalkylalkyl group, a substituted or unsubstituted C3-C30cycloalkenyl group, a substituted or unsubstituted C5-C30 aryl group, asubstituted or unsubstituted C5-C30 arylalkyl group, a substituted orunsubstituted C5-C30 heteroaryl group, a substituted or unsubstitutedC3-C30 heterocyclic ring, a substituted or unsubstituted C4-C30heterocyclolalkyl group, a substituted or unsubstituted C6-C30heteroarylalkyl group or a hydroxyl group; Z, when present, is R or V;and V is independently a polymerizable ethylenically unsaturated organicradical.

Representative examples of urethanes for use herein include, by way ofexample, a secondary amine linked to a carboxyl group which may also belinked to a further group such as an alkyl. Likewise the secondary aminemay also be linked to a further group such as an alkyl .

Representative examples of carbonates for use herein include, by way ofexample, alkyl carbonates, aryl carbonates, and the like.

Representative examples of carbamates, for use herein include, by way ofexample, alkyl carbamates, aryl carbamates, and the like.

Representative examples of carboxyl ureidos, for use herein include, byway of example, alkyl carboxyl ureidos, aryl carboxyl ureidos, and thelike.

Representative examples of sulfonyls for use herein include, by way ofexample, alkyl sulfonyls, aryl sulfonyls, and the like.

Representative examples of alkyl groups for use herein include, by wayof example, a straight or branched hydrocarbon chain radical containingcarbon and hydrogen atoms of from 1 to about 18 carbon atoms with orwithout unsaturation, to the rest of the molecule, e.g., methyl, ethyl,n-propyl, 1-methylethyl(isopropyl), n-butyl, n-pentyl, etc., and thelike.

Representative examples of fluoroalkyl groups for use herein include, byway of example, a straight or branched alkyl group as defined abovehaving one or more fluorine atoms attached to the carbon atom, e.g.,—CF3, —CF2CF3, —CH2CF3, —CH2CF2H, —CF2H and the like.

Representative examples of ester-containing groups for use hereininclude, by way of example, a carboxylic acid ester having one to 20carbon atoms and the like.

Representative examples of ether or polyether containing groups for useherein include, by way of example, an alkyl ether, cycloalkyl ether,cycloalkenyl ether, aryl ether, arylalkyl ether wherein the alkyl,cycloalkyl, cycloalkylalkyl, cycloalkenyl, aryl, and arylalkyl groupsare defined above, e.g., alkylene oxides, poly(alkylene oxide)s such asethylene oxide, propylene oxide, butylene oxide, poly(ethylene oxide)s,poly(ethylene glycol)s, poly(propylene oxide)s, poly(butylene oxide)sand mixtures or copolymers thereof, an ether or polyether group of thegeneral formula —R8OR9, wherein R8 is a bond, an alkyl, cycloalkyl oraryl group as defined above and R9 is an alkyl, cycloalkyl or aryl groupas defined above, e.g., —CH2CH2OC6H5 and —CH2CH2OC2H5, and the like.

Representative examples of amide groups for use herein include, by wayof example, an amide of the general formula —R10C(O)NR11R12 wherein R10,R11 and R12 are independently C1-C30 hydrocarbons, e.g., R10 can bealkylene groups, arylene groups, cycloalkylene groups and R11 and R12can be alkyl groups, aryl groups, and cycloalkyl groups as definedherein and the like.

Representative examples of amine groups for use herein include, by wayof example, an amine of the general formula —R13NR14R15 wherein R13 is aC2-C30 alkylene, arylene, or cycloalkylene and R14 and R15 areindependently C1-C30 hydrocarbons such as, for example, alkyl groups,aryl groups, or cycloalkyl groups as defined herein, and the like.

Representative examples of an ureido group for use herein include, byway of example, an ureido group having one or more substituents orunsubstituted ureido. The ureido group preferably is an ureido grouphaving 1 to 12 carbon atoms. Examples of the substituents include alkylgroups and aryl groups. Examples of the ureido group include3-methylureido, 3,3-dimethylureido, and 3-phenylureido.

Representative examples of alkoxy groups for use herein include, by wayof example, an alkyl group as defined above attached via oxygen linkageto the rest of the molecule, i.e., of the general formula —OR20, whereinR20 is an alkyl, cycloalkyl, cycloalkenyl, aryl or an arylalkyl asdefined above, e.g., —OCH3, —OC2H5, or —OC6H5, and the like.

Representative examples of cycloalkyl groups for use herein include, byway of example, a substituted or unsubstituted non-aromatic mono ormulticyclic ring system of about 3 to about 18 carbon atoms such as, forexample, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,hydronapththyl, adamantyl and norbornyl groups bridged cyclic group orsprirobicyclic groups, e.g., sprio-(4,4)-non-2-yl and the like,optionally containing one or more heteroatoms, e.g., O and N, and thelike.

Representative examples of cycloalkylalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted cyclicring-containing radical containing from about 3 to about 18 carbon atomsdirectly attached to the alkyl group which are then attached to the mainstructure of the monomer at any carbon from the alkyl group that resultsin the creation of a stable structure such as, for example,cyclopropylmethyl, cyclobutylethyl, cyclopentylethyl and the like,wherein the cyclic ring can optionally contain one or more heteroatoms,e.g., O and N, and the like.

Representative examples of cycloalkenyl groups for use herein include,by way of example, a substituted or unsubstituted cyclic ring-containingradical containing from about 3 to about 18 carbon atoms with at leastone carbon-carbon double bond such as, for example, cyclopropenyl,cyclobutenyl, cyclopentenyl and the like, wherein the cyclic ring canoptionally contain one or more heteroatoms, e.g., O and N, and the like.

Representative examples of aryl groups for use herein include, by way ofexample, a substituted or unsubstituted monoaromatic or polyaromaticradical containing from about 5 to about 25 carbon atoms such as, forexample, phenyl, naphthyl, tetrahydronapthyl, indenyl, biphenyl and thelike, optionally containing one or more heteroatoms, e.g., O and N, andthe like.

Representative examples of arylalkyl groups for use herein include, byway of example, a substituted or unsubstituted aryl group as definedabove directly bonded to an alkyl group as defined above, e.g.,—CH2C6H5, —C2H5C6H5 and the like, wherein the aryl group can optionallycontain one or more heteroatoms, e.g., O and N, and the like.

Representative examples of fluoroaryl groups for use herein include, byway of example, an aryl group as defined above having one or morefluorine atoms attached to the aryl group.

Representative examples of heterocyclic ring groups for use hereininclude, by way of example, a substituted or unsubstituted stable 3 toabout 15 membered ring radical, containing carbon atoms and from one tofive heteroatoms, e.g., nitrogen, phosphorus, oxygen, sulfur andmixtures thereof. Suitable heterocyclic ring radicals for use herein maybe a monocyclic, bicyclic or tricyclic ring system, which may includefused, bridged or spiro ring systems, and the nitrogen, phosphorus,carbon, oxygen or sulfur atoms in the heterocyclic ring radical may beoptionally oxidized to various oxidation states. In addition, thenitrogen atom may be optionally quaternized; and the ring radical may bepartially or fully saturated (i.e., heteroaromatic or heteroarylaromatic). Examples of such heterocyclic ring radicals include, but arenot limited to, azetidinyl, acridinyl, benzodioxolyl, benzodioxanyl,benzofurnyl, carbazolyl, cinnolinyl, dioxolanyl, indolizinyl,naphthyridinyl, hydroazepinyl, phenazinyl, phenothiazinyl, phenoxazinyl,phthalazinyl, pyridyl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl,quinolinyl, isoquinolinyl, tetrazoyl, imidazolyl, tetrahydroisouinolyl,piperidinyl, piperazinyl, 2-oxopiazinyl, 2-oxopiidinyl,2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, pyrrolyl, 4-piidonyl,pyrrolidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolinyl,oxasolidinyl, triazolyl, indanyl, isoxazolyl, isoxasolidinyl,morpholinyl, thiazolyl, thiazolinyl, thiazolidinyl, isothiazolyl,quinuclidinyl, isothiazolidinyl, indolyl, isoindolyl, indolinyl,isoindolinyl, octahydroindolyl, octahydroisoindolyl, quinolyl,isoquinolyl, decahydroisoquinolyl, benzimidazolyl, thiadiazolyl,benzopyranyl, benzothiazolyl, benzooxazolyl, furyl, tetrahydrofurtyl,tetrahydropyranyl, thienyl, benzothienyl, thiamorpholinyl,thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, dioxaphospholanyl,oxadiazolyl, chromanyl, isochromanyl and the like and mixtures thereof.

Representative examples of heteroaryl groups for use herein include, byway of example, a substituted or unsubstituted heterocyclic ring radicalas defined above. The heteroaryl ring radical may be attached to themain structure at any heteroatom or carbon atom that results in thecreation of a stable structure.

Representative examples of heteroarylalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted heteroarylring radical as defined above directly bonded to an alkyl group asdefined above. The heteroarylalkyl radical may be attached to the mainstructure at any carbon atom from the alkyl group that results in thecreation of a stable structure.

Representative examples of heterocyclo groups for use herein include, byway of example, a substituted or unsubstituted heterocylic ring radicalas defined above. The heterocyclo ring radical may be attached to themain structure at any heteroatom or carbon atom that results in thecreation of a stable structure.

Representative examples of heterocycloalkyl groups for use hereininclude, by way of example, a substituted or unsubstituted heterocylicring radical as defined above directly bonded to an alkyl group asdefined above. The heterocycloalkyl radical may be attached to the mainstructure at carbon atom in the alkyl group that results in the creationof a stable structure.

Representative examples of a “polymerizable ethylenically unsaturatedorganic radicals” include, by way of example, (meth)acrylate-containingradicals, (meth)acrylamide-containing radicals,vinylcarbonate-containing radicals, vinylcarbamate-containing radicals,styrene-containing radicals and the like. In one embodiment, apolymerizable ethylenically unsaturated organic radical can berepresented by the general formula:

wherein R21 is hydrogen, fluorine or methyl; R22 is independentlyhydrogen, fluorine, or a —CO—Y—R24 radical wherein Y is —O—, —S— or —NH—and R24 is a divalent alkylene radical having 1 to about 10 carbonatoms.

The substituents in the ‘substituted alkyl’, ‘substituted alkoxy’,‘substituted cycloalkyl’, ‘substituted cycloalkylalkyl’, ‘substitutedcycloalkenyl’, ‘substituted arylalkyl’, ‘substituted aryl’, ‘substitutedheterocyclic ring’, ‘substituted heteroaryl ring,’ ‘substitutedheteroarylalkyl’, ‘substituted heterocycloalkyl ring’, ‘substitutedcyclic ring’ and ‘substituted carboxylic acid derivative’ may be thesame or different and include one or more substituents such as hydrogen,hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio(═S),substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy,substituted or unsubstituted alkenyl, substituted or unsubstitutedalkynyl, substituted or unsubstituted aryl, substituted or unsubstitutedarylalkyl, substituted or unsubstituted cycloalkyl, substituted orunsubstituted cycloalkenyl, substituted or unsubstituted amino,substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, substituted heterocycloalkyl ring, substituted orunsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclicring, substituted or unsubstituted guanidine, —COORx, —C(O)Rx, —C(S)Rx,—C(O)NRxRy, —C(O)ONRxRy, —NRxCONRyRz, —N(Rx)SORy, —N(Rx)SO2Ry,—(═N—N(Rx)Ry), —NRxC(O)ORy, —NRxRy, —NRxC(O)Ry-, —NRxC(S)Ry—NRxC(S)NRyRz, —SONRxRy-, —SO2NRxRy-, —ORx, —ORxC(O)NRyRz, —ORxC(O)ORy-,—OC(O)Rx, —OC(O)NRxRy, —RxNRyC(O)Rz, —RxORy, —RxC(O)ORy, —RxC(O)NRyRz,—RxC(O)Rx, —RxOC(O)Ry, —SRx, —SORx, —SO2Rx, —ONO2, wherein Rx, Ry and Rzin each of the above groups can be the same or different and can be ahydrogen atom, substituted or unsubstituted alkyl, substituted orunsubstituted alkoxy, substituted or unsubstituted alkenyl, substitutedor unsubstituted alkynyl, substituted or unsubstituted aryl, substitutedor unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl,substituted or unsubstituted cycloalkenyl, substituted or unsubstitutedamino, substituted or unsubstituted aryl, substituted or unsubstitutedheteroaryl, ‘substituted heterocycloalkyl ring’ substituted orunsubstituted heteroarylalkyl, or a substituted or unsubstitutedheterocyclic ring.

A schematic representation of a synthetic method for making the novelcationic fluorinated poly(ether)-containing monomers disclosed herein isprovided below:

In a second aspect, the invention includes articles formed of deviceforming monomer mixes comprising the monomers of formula (1). Accordingto preferred embodiments, the article is the polymerization product of amixture comprising the aforementioned cationic monomer and at least asecond monomer. Preferred articles are optically clear and useful as acontact lens.

Useful articles made with these materials may require hydrophobic,possibly silicon containing monomers. Preferred compositions have bothhydrophilic and hydrophobic monomers. The invention is applicable to awide variety of polymeric materials, either rigid or soft. Especiallypreferred polymeric materials are lenses including contact lenses,phakic and aphakic intraocular lenses and corneal implants although allpolymeric materials including biomaterials are contemplated as beingwithin the scope of this invention. Especially preferred are siliconcontaining hydrogels.

The present invention also provides medical devices such as heart valvesand films, surgical devices, vessel substitutes, intrauterine devices,membranes, diaphragms, surgical implants, blood vessels, artificialureters, artificial breast tissue and membranes intended to come intocontact with body fluid outside of the body, e.g., membranes for kidneydialysis and heart/lung machines and the like, catheters, mouth guards,denture liners, ophthalmic devices, and especially contact lenses.

Silicon containing hydrogels are prepared by polymerizing a mixturecontaining at least one silicon-containing monomer and at least onehydrophilic monomer. The silicon-containing monomer may function as acrosslinking agent (a crosslinker being defined as a monomer havingmultiple polymerizable functionalities) or a separate crosslinker may beemployed.

An early example of a silicon-containing contact lens material isdisclosed in U.S. Pat. No. 4,153,641 (Deichert et al assigned to Bausch& Lomb Incorporated). Lenses are made from poly(organosiloxane) monomerswhich are α, ω terminally bonded through a divalent hydrocarbon group toa polymerized activated unsaturated group. Various hydrophobicsilicon-containing prepolymers such as 1,3-bis(methacryloxyalkyl)polysiloxanes are copolymerized with known hydrophilic monomers such as2-hydroxyethyl methacrylate (HEMA).

U.S. Pat. No. 5,358,995 (Lai et al) describes a silicon containinghydrogel which is comprised of an acrylic ester-capped polysiloxaneprepolymer, polymerized with a bulky polysiloxanylalkyl(meth)acrylatemonomer, and at least one hydrophilic monomer. Lai et al is assigned toBausch & Lomb Incorporated and the entire disclosure is incorporatedherein by reference. The acrylic ester-capped polysiloxane prepolymer,commonly known as M₂D_(x) consists of two acrylic ester end groups and“x” number of repeating dimethylsiloxane units. The preferred bulkypolysiloxanylalkyl(meth)acrylate monomers are TRIS-type(methacryloxypropyl tris(trimethylsiloxy)silane) with the hydrophilicmonomers being either acrylic- or vinyl-containing.

Other examples of silicon-containing monomer mixtures which may be usedwith this invention include the following: vinyl carbonate and vinylcarbamate monomer mixtures as disclosed in U.S. Pat. Nos. 5,070,215 and5,610,252 (Bambury et al); fluorosilicon monomer mixtures as disclosedin U.S. Pat. Nos. 5,321,108; 5,387,662 and 5,539,016 (Kunzler et al);fumarate monomer mixtures as disclosed in U.S. Pat. Nos. 5,374,662;5,420,324 and 5,496,871 (Lai et al) and urethane monomer mixtures asdisclosed in U.S. Pat. Nos. 5,451,651; 5,648,515; 5,639,908 and5,594,085 (Lai et al), all of which are commonly assigned to assigneeherein Bausch & Lomb Incorporated, and the entire disclosures of whichare incorporated herein by reference.

Examples of non-silicon hydrophobic materials include alkyl acrylatesand methacrylates.

The cationic silicon-containing monomers may be copolymerized with awide variety of hydrophilic monomers to produce silicon hydrogel lenses.Suitable hydrophilic monomers include: unsaturated carboxylic acids,such as methacrylic and acrylic acids; acrylic substituted alcohols,such as 2-hydroxyethylmethacrylate and 2-hydroxyethylacrylate; vinyllactams, such as N-vinylpyrrolidone (NVP) and 1-vinylazonan-2-one; andacrylamides, such as methacrylamide and N,N-dimethylacrylamide (DMA).

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

Hydrophobic cross linkers would include methacrylates such as ethyleneglycol dimethacrylate (EGDMA) and allyl methacrylate (AMA). In contrastto traditional silicon hydrogel monomer mixtures, the monomer mixturescontaining the quaternized silicon monomer of the invention herein arerelatively water soluble. This feature provides advantages overtraditional silicon hydrogel monomer mixtures in that there is less riskof incompatibility phase separation resulting in hazy lenses and thepolymerized materials are extractable with water. However, when desiredtraditional organic extraction methods may also be used. In addition,the extracted lenses demonstrate a good combination of oxygenpermeability (Dk) and low modulus, properties known to be important toobtaining desirable contact lenses. Moreover, lenses prepared with thequaternized silicon monomers of the invention herein are wettable evenwithout surface treatment, provide dry mold release, do not requiresolvents in the monomer mix (although solvents such as glycerol may beused), the extracted polymerized material is not cytotoxic and thesurface is lubricious to the touch. In cases where the polymerizedmonomer mix containing the quaternized silicon monomers of the inventionherein do not demonstrate a desirable tear strength, toughening agentssuch as TBE (4-t-butyl-2-hydroxycyclohexyl methacrylate) may be added tothe monomer mix. Other strengthening agents are well known to those ofordinary skill in the art and may also be used when needed.

Although an advantage of the cationic fluorinated poly(ether)-containingmonomers disclosed herein is that they are relatively compatible withhydrophilic comonomers, an organic diluent may be included in theinitial monomeric mixture. As used herein, the term “organic diluent”encompasses organic compounds which minimize incompatibility of thecomponents in the initial monomeric mixture and are substantiallynonreactive with the components in the initial mixture. Additionally,the organic diluent serves to minimize phase separation of polymerizedproducts produced by polymerization of the monomeric mixture. Also, theorganic diluent will generally be relatively non-inflammable.

Contemplated organic diluents include tert-butanol (TBA); diols, such asethylene glycol and polyols, such as glycerol. Preferably, the organicdiluent is sufficiently soluble in the extraction solvent to facilitateits removal from a cured article during the extraction step. Othersuitable organic diluents would be apparent to a son of ordinary skillin the art.

The organic diluent is included in an amount effective to provide thedesired effect. Generally, the diluent is included at 5 to 60% by weightof the monomeric mixture, with 10 to 50% by weight being especiallypreferred.

According to the present process, the monomeric mixture, comprising atleast one hydrophilic monomer, at least one cationic silicon-containingmonomer and optionally the organic diluent, is shaped and cured byconventional methods such as static casting or spincasting.

Lens formation can be by free radical polymerization such asazobisisobutyronitrile (AIBN) and oxide catalysts using initiators andunder conditions such as those set forth in U.S. Pat. No. 3,808,179,incorporated herein by reference. Photo initiation of polymerization ofthe monomer mixture as is well known in the art may also be used in theprocess of forming an article as disclosed herein. Colorants and thelike may be added prior to monomer polymerization.

Subsequently, a sufficient amount of unreacted monomer and, whenpresent, organic diluent is removed from the cured article to improvethe biocompatibility of the article. Release of non-polymerized monomersinto the eye upon installation of a lens can cause irritation and otherproblems.

Once the biomaterials formed from the polymerized monomer mix containingthe cationic silicon containing monomers disclosed herein are formedthey are then extracted to prepare them for packaging and eventual use.Extraction is accomplished by exposing the polymerized materials tovarious solvents such as water, tert-butanol, etc. for varying periodsof time. For example, one extraction process is to immerse thepolymerized materials in water for about three minutes, remove the waterand then immerse the polymerized materials in another aliquot of waterfor about three minutes, remove that aliquot of water and then autoclavethe polymerized material in water or buffer solution.

Following extraction of unreacted monomers and any organic diluent, theshaped article, for example an RGP lens, is optionally machined byvarious processes known in the art. The machining step includes lathecutting a lens surface, lathe cutting a lens edge, buffing a lens edgeor polishing a lens edge or surface. The present process is particularlyadvantageous for processes wherein a lens surface is lathe cut, sincemachining of a lens surface is especially difficult when the surface istacky or rubbery.

Generally, such machining processes are formed before the article isreleased from a mold part. After the machining operation, the lens canbe released from the mold part and hydrated. Alternately, the articlecan be machined after removal from the mold part and then hydrated.

EXAMPLES

All solvents and reagents are obtained from Sigma-Aldrich, Milwaukee,Wis., and used as received with the exception of the fluorinatedpoly(ether)s, under trade name ZDOL, obtained from Solvay Solexis,Thorofare, N.J., which is used without further purification. Themonomers 2-hydroxyethyl methacrylate and 1-vinyl-2-pyrrolidone arepurified using standard techniques.

Analytical Measurements

NMR: ¹H-Nuclear Magnetic Resonance (NMR) characterization is carried outusing a 400 MHz Varian spectrometer using standard techniques in theart. Samples are dissolved in chloroform-d (99.8 atom % D), unlessotherwise noted. Chemical shifts are determined by assigning theresidual chloroform peak at 7.25 ppm. Peak areas and proton ratios aredetermined by integration of baseline separated peaks. Splittingpatterns (s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet,br=broad) and coupling constants (J/Hz) are reported when present andclearly distinguishable.

SEC: Size Exclusion Chromatography (SEC) analyses are carried out byinjection of 100 μL of sample dissolved in tetrahydrofuran (THF) (5-20mg/mL) onto a Polymer Labs PL Gel Mixed Bed E (×2) column at 35° C.using a Waters 515 HPLC pump and HPLC grade THF mobile phase flow rateof 1.0 mL/min, and detected by a Waters 410 Differential Refractometerat 35° C. Values of M_(n), M_(w), and polydispersity (PD) are determinedby comparison to Polymer Lab Polystyrene narrow standards.

ESI-TOF MS: The electrospray (ESI) time of flight (TOF) MS analysis isformed on an Applied Biosystems Mariner instrument. The instrumentoperated in positive ion mode. The instrument is mass calibrated with astandard solution containing lysine, angiotensinogen, bradykinin(fragment 1-5) and des-Pro bradykinin. This mixture provides aseven-point calibration from 147 to 921 m/z. The applied voltageparameters are optimized from signal obtained from the same standardsolution.

Stock solutions of the polymer samples are prepared as 1 mg/mL intetrahydrofuran (THF). From these stock solutions, samples are preparedfor ESI-TOF MS analysis as 30 μM solutions in isopropanol (IPA) with theaddition of 2% by volume saturated NaCl in IPA. Samples are directlyinfused into the ESI-TOF MS instrument at a rate of 35 μL/min.

Mechanical properties and Oxygen permeability: Modulus and elongationtests are conducted according to ASTM D-1708a, employing an Instron(Model 4502) instrument where the hydrogel film sample is immersed inborate buffered saline; an appropriate size of the film sample is gaugelength 22 mm and width 4.75 mm, where the sample further has endsforming a dog bone shape to accommodate gripping of the sample withclamps of the Instron instrument, and a thickness of 200+50 microns.

Oxygen permeability (also referred to as Dk) is determined by thefollowing procedure. Other methods and/or instruments may be used aslong as the oxygen permeability values obtained therefrom are equivalentto the described method. The oxygen permeability of silicon-containinghydrogels is measured by the polarographic method (ANSI Z80.20-1998)using an O₂ Permeometer Model 201T instrument (Createch, Albany, Calif.USA) having a probe containing a central, circular gold cathode at itsend and a silver anode insulated from the cathode. Measurements aretaken only on pre-inspected pinhole-free, flat silicon-containinghydrogel film samples of three different center thicknesses ranging from150 to 600 microns. Center thickness measurements of the film samplesmay be measured using a Rehder ET-1 electronic thickness gauge.Generally, the film samples have the shape of a circular disk.Measurements are taken with the film sample and probe immersed in a bathcontaining circulating phosphate buffered saline (PBS) equilibrated at35° C.+/−0.2°. Prior to immersing the probe and film sample in the PBSbath, the film sample is placed and centered on the cathode premoistenedwith the equilibrated PBS, ensuring no air bubbles or excess PBS existsbetween the cathode and the film sample, and the film sample is thensecured to the probe with a mounting cap, with the cathode portion ofthe probe contacting only the film sample. For silicon-containinghydrogel films, it is frequently useful to employ a Teflon polymermembrane, e.g., having a circular disk shape, between the probe cathodeand the film sample. In such cases, the Teflon membrane is first placedon the pre-moistened cathode, and then the film sample is placed on theTeflon membrane, ensuring no air bubbles or excess PBS exists beneaththe Teflon membrane or film sample. Once measurements are collected,only data with correlation coefficient value (R2) of 0.97 or highershould be entered into the calculation of Dk value. At least two Dkmeasurements thickness, and meeting R2 value, are obtained. Using knownregression analyses, oxygen permeability (Dk) is calculated from thefilm samples having at least three different thicknesses. Any filmsamples hydrated with solutions other than PBS are first soaked inpurified water and allowed to equilibrate for at least 24 hours, andthen soaked in PHB and allowed to equilibrate for at least 12 hours. Theinstruments are regularly cleaned and regularly calibrated using RGPstandards. Up and lower limits are established by calculating a +/−8.8%of the Repository values established by William J. Benjamin, et al., TheOxygen permeability of Reference Materials, Optom Vis Sci 7 (12s): 95(1997), the disclosure of which is incorporated herein in its entirety:

Repository Material Name Values Lower Limit Upper Limit Fluoroperm 3026.2 24 29 Menicon EX 62.4 56 66 Quantum II 92.9 85 101

Abbreviations NVP 1-Vinyl-2-pyrrolidone TRISMethacryloxypropyltris(trimethylsiloxy)silane HEMA 2-Hydroxyethylmethacrylate

v-64 2,2′-Azobis(2-methylpropionitrile)

PG 1,3-Propanediol EGDMA Ethylene glycol dimethacrylate SA2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate IMVT1,4-bis[4-(2-methacryloxyethyl)phenylamino]anthraquinone Unlessotherwise specifically stated or made clear by its usage, all numbersused in the examples should be considered to be modified by the term“about” and to be weight cent. Example 1 Synthesis of BromoethylTerminated PFPE

To a solution of fluorinated polyether (FOMBLIN (R) ZDOL, SolvaySolexis, 1950 g/mol, 7.01 g) and 2-bromoethylisocyanate (0.65 mL, 7.2mmol) in 1,1,2-trichloro-trifluoroethane (7 mL) was treated with 3 dropsof tin dilaurate and the solution was allowed to stir overnight. Theresulting mixture was filtered through a 0.5 um PTFE filter and solventsremoved under reduced pressure to afford 7.07 g of product.

Example 2 Synthesis of Methacrylate Ammonium Bromide Terminated PFPE

The product from example 1 was dissolved in a mixture of ethyl acetateand α, α, α-trifluorotoluene and treated withN,N-dimethylaminoethylmethacrylate (1.6 mL) and heated until sufficientconversion as monitored by proton NMR spectroscopy was obtained. Solventcan then be removed at reduced pressure. The structure of the cationic,polymerizable fluorinated poly(ether) was confirmed by ESI-MS.

Examples 3-11 Polymerization and Processing of Films Containing ofPrepolymers

Liquid monomer solutions containing fluorinated polyether monomer fromexample 2 above, along with other monomers and additives common toophthalmic materials (diluent, initiator, etc.) can be clamped betweensilanized glass plates at various thicknesses and polymerized usingthermal decomposition of the free radical generating additive by heating2 h at 100° C. under a nitrogen atmosphere.

Contemplated formulations are listed in table 1.

TABLE 1 Example Example 2 NVP HEMA TRIS HFIPMA PG EGDMA ν-64 3 10.0 0.010.0 50.0 25.0 4.0 0.5 0.5 4 10.0 20.0 0.0 45.0 20.0 4.0 0.5 0.5 5 25.025.0 10.0 0.0 35.0 4.0 0.5 0.5 6 10.0 50.0 10.0 25.0 0.0 4.0 0.5 0.5 710.0 25.0 10.0 25.0 25.0 0.0 0.5 0.5 8 10.0 25.0 10.0 25.5 25.0 4.0 0.00.5 9 35.0 50.0 10.0 0.0 0.0 4.0 0.5 0.5 10 45.0 50.5 0.0 0.0 0.0 4.00.0 0.5

Example 11

Films are removed from glass plates and hydrated/extracted in deionizedH₂O for a minimum of 4 h, transferred to fresh deionized H₂O andautoclaved 30 min at 121° C. The cooled films are then analyzed forselected properties of interest in ophthalmic materials as described.Mechanical tests are conducted in borate buffered saline according toASTM D-1708a, discussed above. The oxygen permeabilities, reported in Dk(or barrer) units, are measured in phosphate buffered saline at 35° C.,using acceptable films with three different thicknesses, as discussedabove.

Example 12 Polymerization and Processing of Ophthalmic Lenses ContainingFluorinated Polyether Monomer

40 uL aliquots of a soluble, liquid monomer mix containing 13.9 parts byweight of the product from example 2, 23.3 parts TRIS, 41.8 parts NVP,13.9 parts HEMA, 5 parts PG, 0.5 parts v-64, 1.5 parts SA, and 60 ppmIMVT are sealed between poly(propylene) anterior and posterior contactlens moulds under an inert nitrogen atmosphere, transferred to an ovenand heated under an inert nitrogen atmosphere 2 h at 100° C. The cooledmold pairs are separated and the dry lens released from the mold,hydrated/extracted twice in deionized H2O for a minimum of 3 min,transferred to and sealed in an autoclave vial containing a bufferedsaline solution and autoclaved 30 min at 121° C.

1. A monomer of formula (I):

wherein L can be the same or different and is selected from the groupconsisting of a bond, hydrogen, urethanes, carbonates, carbamates,carboxyl ureidos, sulfonyls, a straight or branched C1-C30 alkyl group,a C1-C30 fluoroalkyl group, a C1-C20 ester-containing group, an alkylether, cycloalkyl ether, cycloalkenyl ether, aryl ether, arylalkylether, a polyether containing group, an ureido group, an amide group, anamine group, a substituted or unsubstituted C1-C30 alkoxy group, asubstituted or unsubstituted C3-C30 cycloalkyl group, a substituted orunsubstituted C3-C30 cycloalkylalkyl group, a substituted orunsubstituted C3-C30 cycloalkenyl group, a substituted or unsubstitutedC5-C30 aryl group, a substituted or unsubstituted C5-C30 arylalkylgroup, a substituted or unsubstituted C5-C30 heteroaryl group, asubstituted or unsubstituted C3-C30 heterocyclic ring, a substituted orunsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group, a C5-C30 fluoroaryl group,or a hydroxyl substituted alkyl ether and combinations thereof; X⁻ is atleast a single charged counter ion; m is 1-5, and n is 1-10,000; each Rfis independently hydrogen, fluorine, a C5-C30 fluoroaryl group, a C1-C30fluoroalkyl group, or combinations thereof with the proviso that atleast some, but not all, Rf is hydrogen; R is independently hydrogen, astraight or branched C1-C30 alkyl group, a C1-C20 ester-containinggroup, an alkyl ether, cycloalkyl ether, cycloalkenyl ether, aryl ether,arylalkyl ether, a polyether containing group, an ureido group, an amidegroup, an amine group, a substituted or unsubstituted C1-C30 alkoxygroup, a substituted or unsubstituted C3-C30 cycloalkyl group, asubstituted or unsubstituted C3-C30 cycloalkylalkyl group, a substitutedor unsubstituted C3-C30 cycloalkenyl group, a substituted orunsubstituted C5-C30 aryl group, a substituted or unsubstituted C5-C30arylalkyl group, a substituted or unsubstituted C5-C30 heteroaryl group,a substituted or unsubstituted C3-C30 heterocyclic ring, a substitutedor unsubstituted C4-C30 heterocyclolalkyl group, a substituted orunsubstituted C6-C30 heteroarylalkyl group or a hydroxyl group; Z, whenpresent, is R or V; and V is independently a polymerizable ethylenicallyunsaturated organic radical.
 2. The monomer of claim 1 wherein X⁻ isselected from the group consisting of Cl⁻, Br⁻, I⁻, CF₃CO₂ ⁻, CH₃CO₂ ⁻,HCO₃ ⁻, CH₃SO₄ ⁻, p-toluenesulfonate, HSO₄ ⁻, H₂PO₄ ⁻, NO₃ ⁻,CH₃CH(OH)CO₂ ⁻, SO₄ ²⁻, CO₃ ²⁻, HPO₄ ²⁻ and mixtures thereof.
 3. Themonomer of claim 1 wherein X⁻ is at least a single charged counter ionand is selected from the group consisting of Cl⁻, Br⁻, I⁻, CF₃CO₂ ⁻,CH₃CO₂ ⁻, HCO₃ ⁻, CH₃SO₄ ⁻, p-toluenesulfonate, HSO₄ ⁻, H₂PO₄ ⁻, NO₃ ⁻,and CH₃CH(OH)CO₂ ⁻ and mixtures thereof.
 4. A monomer mix useful formaking polymerized biomaterials comprising at least one monomer of claim1 and at least one second monomer.
 5. The monomer mix of claim 4,further compromising in addition to the second monomer a hydrophobicmonomer and a hydrophilic monomer.
 6. The monomer mix of claim 4 whereinthe second monomer is selected from the group consisting of unsaturatedcarboxylic acids; methacrylic acids, acrylic acids; acrylic substitutedalcohols; 2-hydroxyethylmethacrylate, 2-hydroxyethylacrylate; vinyllactams; N-vinyl pyrrolidone (NVP) N-vinyl caprolactone; acrylamides;methacrylamide, N,N-dimethylacrylamide; methacrylates; ethylene glycoldimethacrylate, methyl methacrylate, allyl methacrylate; hydrophilicvinyl carbonates, hydrophilic vinyl carbamate monomers; hydrophilicoxazolone monomers, 3-methacryloyloxypropyl tris(trimethylsiloxy)silane,ethylene glycol dimethacrylate (EGDMA), allyl methacrylate (AMA) andmixtures thereof.
 7. A device comprising the monomer of claim 1 as apolymerized comonomer.
 8. The device of claim 7 wherein the device is acontact lens.
 9. The device of claim 7 wherein the contact lens is arigid gas permeable contact lens.
 10. The device of claim 7 wherein thelens is a soft contact lens.
 11. The device of claim 7 wherein the lensis a hydrogel contact lens.
 12. The device of claim 7 wherein the lensis an intraocular lens.
 13. The device of claim 12 wherein the lens is aphakic intraocular lens.
 14. The device of claim 12 wherein the lens isan aphakic intraocular lens.
 15. The device of claim 7 wherein thedevice is a corneal implant.
 16. The device of claim 7 wherein thedevice is selected from the group consisting of heart valves,intraocular lenses, films, surgical devices, vessel substitutes,intrauterine devices, membranes, diaphragms, surgical implants, bloodvessels, artificial ureters, artificial breast tissue, membranes forkidney dialysis machines, membranes for heart/lung machines, catheters,mouth guards, denture liners, ophthalmic devices, and contact lenses.17. A method of making a device comprising: providing a monomer mixturecomprising the monomer of claim 1 and at least a second monomer;subjecting the monomer mixture to polymerizing conditions to provide apolymerized device; extracting the polymerized device; and packaging andsterilizing the polymerized device.
 18. The method of claim 17 whereinthe step of extracting is formed with non-flammable solvents.
 19. Themethod of claim 17 wherein the extraction solvent is water.
 20. Afluorinated polyether monomer end-capped with ethylenically unsaturatedcationic hydrophilic groups.